Our laboratory has devoted the past six years to the investigation of vagal and hormonal mechanisms affecting secretory and motor activity in the stomach, pancreas and liver. Interest has centered on endogenous and exogenous physiological and pharmacological effectors, both inhibitory and stimulatory. Work with insulin, 2-DG, histamine, pentagastrin, and standardized meals in normal animals and in some projects in diabetic dogs, has permitted extensive evaluation of the relationships between vagal, gastrin, CCK/PZ, and other gastrointestinal neuro-hormonal mechanisms. Establishment of techniques for pharmacologic continuous vagal stimulation as well as the serum gastrin assay method (Yalow and Berson) now permits us a wide variety of analyses. Our aims are to be directed to the areas in which we have developed our greatest experience and expertise. We propose to investigate further the relative importance of the roles of the vagus and gastrin as well as their complex inter-relationships with other gastrointestinal hormones in upper GI physiology: 1. The role of the antrum and vagal-secretory responses to insulin and 2-DG after partial vagotomy; 2. The role of released vagal-gastrin in bile secretion; 3. The role of the small bowel in gastrin degradation in humans and dogs; 4. The role of the stomach and acid secretion, as well as antral gastrin activity, in homeostatic mechanisms compensating for metabolic (NH4Cl) acidosis.